This patent application claims a benefit of priority from Korean Patent Application No. 1999/26946 filed Jul. 5, 1999, through PCT Application Serial No. PCT/KR00/00716 filed Jul. 4, 2000, the contents of each of which are incorporated herein by reference.
The present invention relates to novel acrylate-type N-methyl E-2-((2-methylphenyl)oxymethyl)-6-methylphenylglyoxyl amide O-methyl oxime represented by the following formula 1, its preparation method and its use as fungicides. The compound of the present invention has not only stronger fungicidal effect on plant pathogens at low concentrations but also broader fungicidal spectrum than the conventional fungicides. Especially, because the compound has excellent systemic and curative effect as well as no toxicity, it can be used an efficacious agricultural fungicide. In addition, the compound of the present invention can be useful as environmental-friendly fungicide capable of causing less environmental pollution fungicide due to its strong fungicidal effect at low concentrations. 
In spite of their strong fungicidal effect, agricultural fungicides currently in use have been a source of problems, because the required amount is ever increasing as tolerance of target plant pathogens increases. Thus, there is a need to develop new fungicides with strong fungicidal effect and broad fungicidal spectrum. Acrylate-type compounds have been developed as an environment-friendly alternative to the conventional fungicides.
The acrylate fungicides currently in use have strong fungicidal effect on pathogenic fungi of plant origin with broad fungicidal spectrum [EP patent No.: 382, 375 (ICIA5504), U.S. Pat. No.: 4,829,085 (BAS490F), EP patent No.: 398,692 (SSE-126)]. There have been continuing developments of more effective acrylate fungicides.
Among those recently developed, alkoxyiminoaceteamide derivatives with two aryl groups and an ether linkage, have been shown to have strong fungicidal effect on pathogenic fungi at low concentrations with broad fungicidal spectrum. The conventional techniques of their use are described in international publication No.: WO 9617851 and WO 9534526, German publication No.: DE 4312637 and DE 4030038, and European publication No.: EP 398692. The inventors of the present invention also had applied for a patent on alkoxyiminoaceteamide derivative compounds (Korean patent application No.: 98-21068)
The inventors of the present invention developed novel acrylate-type N-methyl E-2-((2-methylphenyl)oxymethyl)-6-methylphenylglyoxylamide O-methyl oxime with outstanding fungicidal effect at low concentrations with broad fungicidal spectrum, especially the compound is superior to the conventional fungicides in terms of systemic as well as curative effect.
It is an object of this invention to provide novel acrylate-type N-methyl E-2-((2-methylphenyl)oxymethyl)-6-methylphenylglyoxylamide O-methyl oxime represented by the formula 1.
It is a further object of this invention to provide a method for preparing novel acrylate-type N-methyl E-2-((2-methylphenyl)oxymethyl)-6-methylphenylglyoxylamide O-methyl oxime.
It is an additional object of this invention to provide agricultural fungicides, containing acrylate-type N-methyl E-2-((2-methylphenyl)oxymethyl)-6-methylphenylglyoxylamide O-methyl oxime as an active ingredient.
Hereinafter, the present invention is described in detail.
The present invention provides novel acrylate-type N-methyl E-2-((2-methylphenyl) oxymethyl)-6-methylphenylglyoxyl amide O-methyl oxime represented by the formula 1. 
The acrylate-type compound represented by the formula 1 of the present invention, namely N-methyl E-2-((2-methylphenyl)oxymethyl)-6-methylphenylglyoxylamide O-methyl oxime, shows broad fungicidal spectrum as well as strong fungicidal effect on plant pathogens at low concentrations. The compound also has excellent curative effect and remarkable systemic effect in plant body.
The compound of the present invention is especially superior to the conventional fungicides such as triazole-type flusilazole or acrylate-type kresoxim methyl (BAS490F) in the protection from barley powder mildew and wheat leaf rust at low concentrations. In addition, the compound of the present invention shows remarkable control efficacy on rice blast, tomato late blight and rice sheath blight at low concentrations. Thus, the compound has been shown to be remarkably effective on various kinds of plant pathogens.
The present invention provides a method of preparation for the novel acrylate-type N-methyl E-2-((2-methylphenyl) oxymethyl)-6-methylphenylglyoxylamide O-methyl oxime represented by the formula 1.
The method for preparing the compound according to the present invention is summarized in the following steps.
1) methyl E-2-bromomethyl-6-methylphenylglyoxylate O-methyl oxime is reacted with o-cresol under a basic condition to give methyl E-2-((2-methylphenyl)oxymethyl)-6-methylphenylglyoxylate O-methyl oxime (step 1); and
2) methyl E-2-((2-methylphenyl)oxymethyl)-6-methylphenylglyoxylate O-methyl oxime prepared in the step 1 is reacted with methylamine (NH2Me) to give N-methyl E-2-((2-methylphenyl)oxymethyl)-6-methylphenylglyoxylamide O-methyl oxime of the present invention (step 2).
The preparation of methyl E-2-((2-methylphenyl) oxymethyl)-6-methylphenylglyoxylate O-methyl oxime (formula 2) of the step 1 may be done as in the scheme 1. 
Methyl E-2-bromomethyl-6-methylphenylglyoxylate O-methyl oxime of the formula 3 is reacted with o-cresol of the formula 4 under an appropriate basic condition to give the compound of the formula 2. The base may be preferably selected from the group comprising K2CO2, Na2CO3, triethylamine (TEA) and sodium hydride (NaH), etc. A variety of reaction solvents including dimethylformamide (DMF), tetrahydrofuran (THF), chloroform (CHC3) and etc. may be used. The reaction temperature may be xe2x88x9220xcx9c100xc2x0 C., preferably xe2x88x9210xcx9c30xc2x0 C.
Methyl alkoxyiminoacetate of the formula 2 prepared in the scheme 1 is reacted with methylamine to give N-methyl E-2-((2-methylphenyl)oxymethyl)-6-methylphenylglyoxylamide O-methyl oxime of the formula 1 as represented in the scheme 2. 
In the above reaction, the number of equivalent of methylamine may be 1-10, preferably 5. The reaction solvents are preferably used dimethylforamide (DMF), tetrahydrofuran (THF), chloroform (CHCl3), etc. The reaction temperature may be 0xcx9c100xc2x0 C., preferably 0xcx9c30xc2x0 C.
Methyl E-2-bromomethyl-6-methylphenylglyoxylate O-methyl oxime (formula 3), the reactant of the scheme 1, can be prepared by the method in the scheme 3. 
Methyl 2,6-dimethylphenylglyoxylate of the formula 6 is obtained by the reaction of 2-bromo-m-xylene of the formula 5 with buthyllithium (BuLi), followed by the reaction with dimethyl oxalate [(CO2Me)2]. The compound of the formula 6 is reacted with methoxylamine hydrochloride (MeONH2.HCl) to give methyl E-2,6-dimethylphenylglyoxylate O-methyl oxime of the formula 7 [U.S. Pat. No.: 5,371,223 (1994)]. The compound of the formula 7 is reacted with N-bromosuccinimide (NBS) to give the compound of the formula 3 [U.S. Pat. No.: 5,371,223 (1994); L. Horner Angew. Chem. 71 (1959), 349].
The present invention also provides agricultural fungicides, containing N-methyl E-2-((2-methylphenyl)oxymethyl)-6-methylphenylglyoxylamide O-methyl oxime as an active ingredient.
N-Methyl E-2-((2-methylphenyl)oxymethyl)-6-methylphenyl glyoxylamide O-methyl oxime of the present invention can be a useful agricultural fungicides due to its strong fungicidal effect at low concentrations, broad fungicidal spectrum, especially, excellent curative and systemic effect, and no phytotoxicity.
Agricultural fungicides can be formulated as a single compound of the formula 1, or as a mixture with other compounds to improve the fungicidal effect and to broaden the spectrum of target pathogens.
The compound of the present invention can be used to control and reduce damage in the case of the followings: crops such as rice, wheat, barley, etc.; fruits such as an apple, a pear, an orange, a grape, a banana, a peach, etc.; coffee; tea; vegetables such as a potato, a red pepper, a pimento, a tomato, a cucumber, a watermelon, a melon, a lettuce, a Chinese cabbage, a celery, a rape, a peanut, a cabbage, a green onion, a garlic, a ginger, an onion; a grass; seeding trees for gardens and forestry; and flowers such as a carnation, a lily, a rose, a chrysanthemum, etc. It may also be used for seeds and agricultural products during storage.
The compound of the present invention can be used to control the disease caused by the phytopathogen classified as according to the pathogenic taxonomy in the following genus and species: Pyricularia oryzae, Rhizoctonia solani, Puccinia recondita, Puccinia striiformis, Erysiphe graminis, Sphaerotheca fuliginea, Sphaerotheca macularis, Elsinoe spp., Podosphaera leucotricha, Uncinula necator, Helminthosporium spp., Alternaria spp., Rhynchosporium spp., Septoria spp., Pyrenophora spp., Botryosphaeria dothidea, Pseudocercosporella herpotrichoides, Gaeumannomyces graminis, Cercospora spp., Cercosporidium personata, Botrytis cinerea, Venturia inaequalis, Cladosporium spp., Plasmopara viticola, Bremia lactucae, Peronospora spp., Pseudocercospora humuli, Pseudoperonospora cubensis, Phytophthora infestans, Phytophthora capsici, Phytophthora spp., Penicillium spp., Trichoderma viride, Gloeosporium musarum, Glomerella cingulata, Mycosphaerella melonis, Fusarium spp., and Marssonina mali. 
In particular, the compound of the present invention has excellent fungicidal effect on barley powdery mildew and wheat leaf rust, rice blast, rice sheath blight, cucumber gray mould and tomato late blight, etc.
In addition, the fungicidal compositions of the present invention can be employed in combination with one or more additional known pesticides such as fungicides, plant growth regulators, insecticides and herbicides, and if necessary, fertilizers, in suitable ratio, in order to improve the fungicidal effect or to broaden the spectrum of target pathogen. Such additional pesticides are followed:
1) fungicidesxe2x80x94aldimorph, anilazine, BAS490F, benalaxyl, benomyl, biloxazol, binapacryl, bitertanol, blasticidin S, bromuconazole, bupirimate, buthiobate, captafol, captan, carbendazim, carboxin, chlorothalonil, copper oxychloride, copper sulphate, cycloheximide, cymoxanil, cyproconazole, dichlofluanide, dichlone, diclomezin, dicloran, difenoconazole, dimethomorph, diniconazole, dinocap, dithianon, dodemorph, edifenphos, etaconazole, ethirimol, etridiazole, fenarimol, fenpiclonil, fenpropidin, fenpropimorph, fentin acetate, flutolanil, flutriafol, flusilazole, folpet, fosetyl-aluminium, furalaxyl, guazatin, hexaconazole, hydroxyisoxazole, ICIA5504, imazalil, imibenconazole, iprobenfos, iprodione, isoprothiolane, kasugamycin, mancozeb, maneb, mepanipyrim, mepronil, metalaxyl, methfuroxam, myclobutanil, neoasozin, nuarimol, ofurace, oxadixyl, oxycarboxin, pefurazoate, penconazole, pencycuron, phenazin oxide, phthalide, polyoxinD, polyram, probenazole, prochloraz, procymidone, propamocarb, propiconazole, propineb, prothiocarb, pyrazophos, pyrifenox, pyrrolnitrin, quintozene, SSF-109, SSF-126, streptomycin, tebuconazole, tetraconazole, thiabendazole, thicyofen, thiophanate-methyl, thiram, tolclofos-methyl, triacetate salt of 1,1-iminodi(octamethylene)diguanidine, triadimefon, triadimenol, tricyclazole, tecnazene, tridemorph, triforine, validamycin A, vinclozolin, zarilamid, and zineb;
2) insecticidesxe2x80x94acetamiprid, buprofezin, carbaryl, carbofuran, carbosulfan, chlopyrifos, cycloprothrin, demeton-s-methyl, diazinon, dimethoate, ethofenprox, fenitrothion, fenobucarb, fenthion, fipronil, furathiocarb, imidacloprid, isoprocarb, isoxathion, monocrotophos, phenthoate, pirimicarb, and propaphos;
3) plant growth regulators and herbicidesxe2x80x943,6-dichloropicolinic acid, 1-(4-chlorophenyl)-4,6-dimethyl -2-oxo-1,2-dihydropyridine-3-carboxylic acid, methyl-3,6-dichloroanisate, abscisic acid, asulam, benzoylprop-ethyl, carbetamide, daminozide, difenzoquat, dikegulac, ethephon, fenpentezol, fluoridamid, glyphosate, glyphosine, hydroxybenzonitriles (i.e. bromoxynil), inabenfide, isopyrimol, long chain fatty alcohols and acids, maleic hydrazide, mefluidide, morphactins (i.e. chlorfluoroecol), paclobutrazol, phenoxyacetic acids (i.e. 2,4-D or MCPA), substituted benzoic acid (i.e. triiodobenzoic acid), substituted quaternary ammonium and phosphonium compounds (i.e. chloromequat, chlorphonium or mepiquatchloride), tecnazene, auxins (i.e. indoleacetic acid, indolebutyric acid, and naphthoxyacetic acid), cytokinins (i.e. benzimidazole, benzyladenine, benzyladenopurine, diphenylurea, and kinetin), gibberellins (i.e. GA3, GA4 and GA7), and triapenthenol.
Although the compound of the Dresent invention can be used directly on the plants, it is used mostly in the form of formulations for convenience and stability. The type of formulations may vary depending on the purpose.
The fungicides containing the compound of the present invention can be formulated in forms of wettable powders, emulsifiable concentrates, granules, dustable powders, suspension concentrates, water dispersible granules, up-granules and wettable powders for seed treatment and pastes. The fungicides containing the compound of the present invention as an active compound, can be applied (sprayed or painted) directly to leaves, trunks, branches, roots or seeds of plants including crops, seedlings, shrubs and trees, or in the mixture with a general soil and a seedling culture soil or culture medium for planting of a paddy or a upland field. It may also be used to treat aquiculture medium for the control of phytopathogens.
The fungicidal compositions are preferred to comprise one or more active compounds of the present invention with solid or liquid carriers and various inert ingredients to improve the adhesion and stability of the compounds of the present invention, an active ingredient, and to attain user""s convenience. At this time, the compositions ratio of the compounds according to the present invention is preferred to be 1-90 wt % in the case of wettable powders, emulsifiable concentrates, and wettable powders or suspension concentrates for seed treatment, 0.1-10 wt % in the case of dustable powders, 1-50 wt % in the case of suspension concentrates, 1-30 wt % in the case of granules or up-granules, and less than 25 wt % in the case of a mixture or dressing with fertilizers (i.e. fertilizers containing nitrogen, phosphorus and potassium), and the compositions ratio is variable according to the purposed use of the compositions.
In the formulation for the compound of the present invention as the carriers, the preferred liquid carriers are water, alcohols (i.e. methanol, benzyl alcohol, furfuryl alcohol, butanol, ethylene glycol, glycerin, etc.), ketones (i.e. cyclohexanone, acetone, methylethyl ketone, etc.), ethers (i.e. dioxane, tetrahydrofuran, celosolb, etc.), aliphatic hydrocarbons (i.e. gasoline, kerosene, etc.), halogenated hydrocarbons (i.e. chloroform, carbon tetrachloride, etc.), acid amides (i.e. dimethylformamide, etc.), esters (i.e. ethyl acetate, butyl acetate, ethylene glycol acetate, aliphatic acid glycerin ester, etc.), nitrites (i.e. acetonitrile, etc.) and aromatic hydrocarbons (i.e. benzene, toluene, xylene, etc.). The said carriers can be used as a single or mixture. And the preferred solid carriers are mineral fillers (i.e. kaolin, clay, bentonite, acidic white clay, talc, silica, sand, diatom earth, dolomite, calcium carbonate, powdery magnesium, gypsum, etc.) and vegetable powders (i.e. soybean flour, wheat flour, sawdust, starch flour, crystalline cellulose, etc.).
In addition, the fungicidal compositions of the present invention may include emulsifiers, binders, dispersants, penetrants, and surfactants of anionic, cationic or nonionic type. The cationic surfactants may be long-chained alkyl ammonium salt such as bromo cetyltrimethylammonium salt. The anionic surfactants include alkali metal salts, alkali earth metal salts or ammonium salts of the following compounds: alkylarylsulfonic acid such as dodecylbenzenesulfonic acid; alkyloxysulfonic acid such as lauryloxysulfonic acid; arylsulfonic acids such as ligninsulfonic acid, naphthalenesulfonic acid and dibutyl naphthalenesulfonic acid; laurylether sulfate; aliphatic alcohol sulfate; aliphatic acid; hexadecanol sulfate; heptandecanol sulfate; and glycol ether. The nonionic surfactants include aliphatic alcohols such as oleyl alcohol and cetyl alcohol, caster oil containing phenol, alkyl phenol, ethylene oxide, propylene oxide, and the condensation product of naphthalenesulfonic acid with either phenol or formaldehyde.
The fungicidal compositions for seed treatment may include binders to improve the adhesion, and use N-methylpyrrolidine, propylene glycol or N,N-dimethylformamide as a solvent.